Effects of phorbol, dexamethasone and starvation on 3-O-methyl-D-glucose transport by rat thymocytes. Modulation of transport by altered trans effects.
Uptake of 3-O-methyl-D-glucoside (3-OMG) into thymocytes was studied to ascertain if it is modulated by endofacial hexokinase activity or by intracellular glucose. (1) The Vmax for net uptake of 3-OMG into rat thymocytes is increased by phorbol 12-myristate 13-acetate (PMA; 40 nM) or starvation for 4 h, and decreased by dexamethasone (1 microM). Starvation for 4 h abolishes the PMA-dependent increase in 3-OMG uptake; this effect is prevented by incubation in 2-deoxyglucose (2-dGlc; 1 mM). (2) Dexamethasone decreases 2-dGlc uptake, increases the rate of 2-dGlc exit and decreases accumulation of free 2-dGlc, consistent with decreased endofacial hexokinase activity. (3) 3-OMG uptake is decreased by preloading the cells with 2-dGlc or glucose, whereas preloading with 3-OMG (40 mM) increases uptake of 3-OMG. (4) The inhibitory effect of preloaded 2-dGlc or glucose on 3-OMG uptake is decreased by PMA. (5) Preloading cells with 3-OMG (40 mM) increases 2-dGlc influx in control and dexamethasone-treated cells, but not into PMA-treated cells. (6) The maximal rate of self-exchange of 3-OMG is similar in control, PMA- or dexamethasone-treated cells. These results are consistent with the following view: 3-OMG uptake is retarded by exchange with cytosolic glucose, or 2-dGlc. PMA, by increasing endofacial hexokinase activity, or starvation depletes glucose from the endofacial surface of the transporter, and hence increase 3-OMG uptake. Dexamethasone, by decreasing endofacial hexokinase activity, increases endofacial binding of glucose, and hence decreases 3-OMG uptake. Cytosolic 3-OMG competes with glucose for endofacial sites, and hence the maximal rates of exchange uptake of 3-OMG are similar in control, PMA- or dexamethasone-treated cells, as the activity of thymocyte glucose transporters is apparently unaltered.
Naftalin
R J
RJ
Department of Physiology, King's College London, Strand, U.K.
Rist
R J
RJ
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006600:Hexosephosphates / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D006600:Hexosephosphates; D008757:Methylglucosides; D008759:Methylglycosides; D019325:3-O-Methylglucose; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate